miR-107 regulates tumor progression by targeting NF1 in gastric cancer.
miR-107 regulates tumor progression by targeting NF1 in gastric cancer.
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miR-107通过靶向胃癌中的NF1来调节肿瘤进展
DOI：
10.1038/srep36531
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发表时间：
2016-11-09
影响因子：
4.6
通讯作者：
Wang M
中科院分区：
文献类型：
--
作者：
Wang S;Ma G;Zhu H;Lv C;Chu H;Tong N;Wu D;Qiang F;Gong W;Zhao Q;Tao G;Zhou J;Zhang Z;Wang M
我们先前的全基因组miRNA微阵列研究显示，miR-107在胃癌（GC）中上调。本研究旨在探讨其在胃癌发病机制中的生物学作用。整合在硅预测算法与蛋白质印迹分析显示，miR-107抑制提高NF 1（神经纤维蛋白1）的mRNA和蛋白质水平，表明NF 1是miR-107在GC中的靶点之一。荧光素酶报告基因分析显示，miR-107通过与NF 1 mRNA 3′-UTR的第一个潜在结合位点结合，抑制NF 1的表达。mRNA稳定性分析表明，这种结合可导致NF 1 mRNA的不稳定，这可能是NF 1 mRNA异常表达的原因之一。采用细胞生长、transwell迁移和侵袭实验等功能分析方法研究miR-107与其靶点之间的相互作用对胃癌发生和发展的影响。此外，我们还研究了55例胃癌组织中miR-107的表达与临床表型的关系，发现miR-107的高表达与肿瘤的大小和浸润深度有关。结果显示，下调miR-107可抑制细胞生长、迁移和侵袭，而NF 1抑制可促进这些表型。我们的研究结果提供了miR-107在GC中调节NF 1的机制，并强调了miR-107和NF 1之间的相互作用在GC发展和进展中的重要性。
Our previous genome-wide miRNA microarray study revealed that miR-107 was upregulated in gastric cancer (GC). In this study we aimed to explore its biological role in the pathogenesis of GC. Integratingin silicoprediction algorithms with western blotting assays revealed that miR-107 inhibition enhanced NF1 (neurofibromin 1) mRNA and protein levels, suggesting that NF1 is one of miR-107 targets in GC. Luciferase reporter assay revealed that miR-107 suppressed NF1 expression by binding to the first potential binding site within the 3′-UTR ofNF1mRNA. mRNA stable assay indicated this binding could result inNF1mRNA instability, which might contribute to its abnormal protein expression. Functional analyses such as cell growth, transwell migration and invasion assays were used to investigate the role of interaction between miR-107 and its target on GC development and progression. Moreover, We investigated the association between the clinical phenotype and the status of miR-107 expression in 55 GC tissues, and found the high expression contributed to the tumor size and depth of invasion. The results exhibited that down regulation of miR-107 opposed cell growth, migration, and invasion, whereas NF1 repression promoted these phenotypes. Our findings provide a mechanism by which miR-107 regulates NF1 in GC, as well as highlight the importance of interaction between miR-107 and NF1 in GC development and progression.
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影响因子：
5.6
作者：
Finnerty JR;Wang WX;Hébert SS;Wilfred BR;Mao G;Nelson PT
通讯作者：
Nelson PT
影响因子：
3.5
作者：
Maertens, O;Prenen, H;Legius, E
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6
作者：
Wang, Wang-Xia;Wilfred, Bernard R.;Nelson, Peter T.
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Nelson, Peter T.
影响因子：
3.7
作者：
Lenarduzzi M;Hui AB;Alajez NM;Shi W;Williams J;Yue S;O'Sullivan B;Liu FF
通讯作者：
Liu FF
影响因子：
24.5
作者：
Grady WM;Tewari M
通讯作者：
Tewari M